Three cohorts, each consisting of 165 pairs of male twins aged 11, 18, and 25 will be ascertained from birth records, and recruited, together with their biological parents and a male sibling, where available, to participate in a two-day laboratory assessment. One-third of each cohort will consist of high-risk families in which the biological father has a history of substance abuse (SA); the remainder of each cohort will be unselected. Half of the twin pairs will be monozygotic and half of the MZ and DZ twin families will reside in the Minneapolis-St. Paul metropolitan area and the other half in out-state Minnesota. The assessment will involve structured psychiatric interviews and assessment of substance use, cognitive and neuropsychological tests, inventories of personality, interests, and talents, assessment of psycho- physiological markers associated with SA or with psychiatric disorders that entail risk for SA, and assessment of family and peer group characteristics, and a daily activities diary. The twins and siblings will participate in a one-day follow-up laboratory assessment in the 5th year of the project. It is intended that these twin-families will subsequently be follow-up over a 7 year period. The 165 high-risk families will permit a joint analysis of established and putative risk factors for SA. The 330 unselected twin-families will provide data for multivariate biometrical- genetic analysis of these risk factors in juvenile, late adolescent, and young-adult males. The central purpose of this study is to identify the mechanisms of genotype-environmental covariation and interaction that determined the natural history of substance abuse.